Genotype-targeted local therapy of glioma
| العنوان: | Genotype-targeted local therapy of glioma |
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| المؤلفون: | Kensuke Tateishi, Erik A. Williams, Joshua M. Francis, Jochen K. Lennerz, Anthony J. Iafrate, Julie M. Batten, Hiroaki Wakimoto, Koerner Mva, Fumi Higuchi, Tracy T. Batchelor, Stephen P. Schmidt, Barker Fg nd, Aymen Baig, Gregory R. Wojtkiewicz, Andrew S. Chi, Tai Tammy, Priscilla K. Brastianos, Tristan Penson, Robert Langer, Giovanni Traverso, William T. Curry, Shilpa S. Tummala, Julie J. Miller, Ameya R. Kirtane, Mikael L. Rinne, Jaimie Rogner, Matthew Meyerson, Hormoz Mazdiyasni, Daniel P. Cahill, Avner Fink, Ganesh M. Shankar, Justin T. Jordan, Tareq A. Juratli |
| المصدر: | Proceedings of the National Academy of Sciences. 115 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Operating Rooms, IDH1, Genotype, Nicotinamide phosphoribosyltransferase, IDH2, 03 medical and health sciences, chemistry.chemical_compound, In vivo, Glioma, Humans, Medicine, Precision Medicine, Multidisciplinary, Brain Neoplasms, business.industry, medicine.disease, 030104 developmental biology, Isocitrate dehydrogenase, PNAS Plus, chemistry, Toxicity, Drug delivery, Cancer research, business |
| الوصف: | Aggressive neurosurgical resection to achieve sustained local control is essential for prolonging survival in patients with lower-grade glioma. However, progression in many of these patients is characterized by local regrowth. Most lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) or IDH2 mutations, which sensitize to metabolism-altering agents. To improve local control of IDH mutant gliomas while avoiding systemic toxicity associated with metabolic therapies, we developed a precision intraoperative treatment that couples a rapid multiplexed genotyping tool with a sustained release microparticle (MP) drug delivery system containing an IDH-directed nicotinamide phosphoribosyltransferase (NAMPT) inhibitor (GMX-1778). We validated our genetic diagnostic tool on clinically annotated tumor specimens. GMX-1778 MPs showed mutant IDH genotype-specific toxicity in vitro and in vivo, inducing regression of orthotopic IDH mutant glioma murine models. Our strategy enables immediate intraoperative genotyping and local application of a genotype-specific treatment in surgical scenarios where local tumor control is paramount and systemic toxicity is therapeutically limiting. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2fa56287282c12514babf942cdd1c137 https://doi.org/10.1073/pnas.1805751115 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2fa56287282c12514babf942cdd1c137 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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